chr16-14644480-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016561.3(BFAR):​c.134C>T​(p.Thr45Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,004 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

BFAR
NM_016561.3 missense

Scores

5
5
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.69
Variant links:
Genes affected
BFAR (HGNC:17613): (bifunctional apoptosis regulator) Enables caspase binding activity; protein-macromolecule adaptor activity; and ubiquitin protein ligase activity. Involved in negative regulation of IRE1-mediated unfolded protein response; proteasome-mediated ubiquitin-dependent protein catabolic process; and protein ubiquitination. Acts upstream of or within negative regulation of apoptotic process. Located in endoplasmic reticulum and membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BFARNM_016561.3 linkc.134C>T p.Thr45Ile missense_variant Exon 2 of 8 ENST00000261658.7 NP_057645.1 Q9NZS9-1
BFARNM_001330500.2 linkc.134C>T p.Thr45Ile missense_variant Exon 2 of 6 NP_001317429.1 H3BMP2
BFARXM_005255350.3 linkc.-46C>T 5_prime_UTR_variant Exon 2 of 7 XP_005255407.1 Q9NZS9-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BFARENST00000261658.7 linkc.134C>T p.Thr45Ile missense_variant Exon 2 of 8 1 NM_016561.3 ENSP00000261658.2 Q9NZS9-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152116
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251478
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461888
Hom.:
0
Cov.:
34
AF XY:
0.00000550
AC XY:
4
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000894
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152116
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 17, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.134C>T (p.T45I) alteration is located in exon 2 (coding exon 1) of the BFAR gene. This alteration results from a C to T substitution at nucleotide position 134, causing the threonine (T) at amino acid position 45 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.84
BayesDel_addAF
Benign
0.0060
T
BayesDel_noAF
Uncertain
0.0
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.033
T;T;.;.
Eigen
Uncertain
0.58
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.79
T;T;T;T
M_CAP
Benign
0.051
D
MetaRNN
Uncertain
0.50
D;D;D;D
MetaSVM
Benign
-0.84
T
MutationAssessor
Benign
-0.080
N;.;.;.
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-1.2
N;N;.;N
REVEL
Uncertain
0.37
Sift
Benign
0.11
T;T;.;T
Sift4G
Uncertain
0.011
D;D;D;T
Polyphen
0.99
D;.;.;.
Vest4
0.89
MutPred
0.65
Loss of catalytic residue at T45 (P = 0.0323);Loss of catalytic residue at T45 (P = 0.0323);Loss of catalytic residue at T45 (P = 0.0323);Loss of catalytic residue at T45 (P = 0.0323);
MVP
0.34
MPC
0.56
ClinPred
0.63
D
GERP RS
6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.26
gMVP
0.66

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1329630315; hg19: chr16-14738337; API